Compounds for use in the present invention are thought to inhibit the enzyme phospholipase A2 (PLA2, EC 3.1.1.4). Phospholipase A2 catalyzes the breakdown of phospholipids at the sn-2 position to produce a fatty acid and a lysophospholipid. The activity of this enzyme has been correlated with various cell functions, particularly with the production of lipid mediators such as eicosanoid production (prostaglandins, thromboxanes and leukotrienes), platelet activating factor and lysophospholipids. Compounds for use in the present invention may offer a wider scope of protection of cells and organisms from injurious agents and pathogenic processes, including the prevention and treatment of eye diseases.
The elderly population in the United States is increasing rapidly. By the year 2030, approximately 70 million Americans will be over 65 years of age. Loss of vision among the elderly is a major health care problem: approximately one in three elderly persons has some form of vision-reducing eye disease by the age of 65. Vision impairment is associated with a decreased ability to perform activities of daily living and an increased risk for depression.
Although estimates vary, there are approximately 10 million blind and visually impaired people in the United States, of which approximately 5.5 million are elderly individuals. Cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy are the four eye disorders that pose the greatest threats to vision after age 40. Patients with age-related macular degeneration often have the following symptoms: blurred vision, image distortion, central scotoma, and/or difficulty reading; Patients with glaucoma often have the following symptoms: visual field loss and/or blurred vision (late); Patients with cataracts often complain of blurred vision, glare, and/or monocular diplopia; Patients with diabetic retinopathy often have the following symptoms: Blurred vision, floaters, visual field loss, often have poor night vision.
Other common eye disorders of aging, include presbyopia, dry eye, floaters and flashes, retinal detachment, and eyelid problems such as drooping upper or lower lids.
In the United States, diabetes is responsible for 8% of legal blindness, making it the leading cause of new cases of blindness in adults 20-74 years of age. Each year, between 12,000 to 24,000 people lose their sight because of diabetes, making patients with diabetes 25 times more likely to lose vision than those who are not diabetic, according to the American Academy of Opthalmology. In addition, diabetic retinopathy often leads to additional eye disorders such as retinal detachment, glaucoma cataract, and corneal disease, contributing to the high rate of blindness in diabetics.
Over 29 million people in the United States wear contact lenses, which provide a safe and effective way to correct vision when used with care and proper supervision. However, many contact lens wearers and potential contact lens wearers suffer from discomfort, dry eyes, and infection as a result of contact lens use. There is therefore a need to design contact lenses to comprise compounds that allow the lens to be more biocompatible, comfortable, tear-wettable, anti-bacterial and oxygen permeable.